CRTH2 is a G protein-coupled chemoattractant receptor expressed on Th2 cells (Nagata et al., J. Immunol., 1999, 162, 1278-1286), eosinophils, and basophils (Hirai et al., J. Exp. Med., 2001, 193, 255-261). Prostaglandin D2 (PGD2) is a natural ligand for CRTH2, and is the major inflammatory mediator produced from mast cells. It has been shown that activation of CRTH2 by PGD2 induces migration and activation of Th2 cells (Hirai et al., J. Exp. Med. 2001, 193, 255-261; Gervais et al., J. Allergy Clin. Immunol. 2001, 108, 982-988) which in turn are involved in the orchestration of an allergic inflammatory response by directly or indirectly inducing migration, activation, priming and prolonged survival of effector cells, such as eosinophils and basophils (Sanz et al., J. Immunol. 1998, 160, 5637-5645; Pope et al., J. Allergy Clin. Immunol. 2001, 108, 594-601; Teran L. M., Clin. Exp. Allergy 1999, 29, 287-290). The role of PGD2 in the initiation and maintenance of allergic inflammation has also been demonstrated in mouse models of asthma by showing that overproduction of PGD2 in vivo by PGD2 synthase exacerbates airway inflammation (Fujitani et al., J. Immunol. 2002, 168, 443-449).
Accordingly, compounds which are modulators, preferably inhibitors, of the interaction between CRTH2 and PGD2 should be useful for the treatment of diseases and disorders that are mediated by CRTH2, PGD2, Th2 cells, eosinophils, and/or basophils. These diseases include but are not limited to allergic disorders, asthmatic disorders, and inflammatory disorders such as allergic rhinitis, allergic asthma, bronchoconstriction, atopic dermatitis and systemic inflammatory disorders.